Peptidoglycan pentapeptide precursor terminating in L-lysine-D-alanine-D-alanine

The **peptidoglycan pentapeptide precursor terminating in L-lysine-D-alanine-D-alanine** is a conserved structural motif at the end of the peptide stems in nascent bacterial cell wall (peptidoglycan) biosynthesis, particularly in Gram-positive cocci. The consensus sequence is **L-Ala-γ-D-Glu-L-Lys-D-Ala-D-Ala** attached to a muramyl glycan backbone[1][2]. This terminal D-Ala-D-Ala sequence is the direct physiological target for **glycopeptide antibiotics** such as vancomycin, which bind and sequester this motif to inhibit the critical process of peptidoglycan cross-linking by bacterial transpeptidases (penicillin-binding proteins). Structural alteration of this terminus (e.g., to D-Ala-D-Lac) is a major resistance mechanism in vancomycin-resistant enterococci[3][7]. As a chemical entity, it is not a protein or classic "drug target" but a peptide/structural epitope essential for bacterial viability and selective antibiotic action.\n\n**Note:** This entity is *not* a protein receptor, enzyme, or transporter, but a motif in a larger macromolecular structure. Its recognition as a drug target is by virtue of it being the molecular site of action for several major antibiotic classes. \n**No canonical abbreviation** (e.g., gene/protein symbol) exists, as it is a repeating peptide sequence, not a gene product.

Other names

Peptidoglycan D-Ala-D-Ala terminusPeptidoglycan precursor pentapeptide (Lys-type)

Glycopeptide antibiotics (e.g., vancomycin) bind directly to the D-Ala-D-Ala terminus of the uncrosslinked peptidoglycan precursor, preventing transpeptidase-mediated cross-linking and thus blocking cell wall synthesis[3][7].\nß-lactam antibiotics inhibit the transpeptidase enzymes (penicillin-binding proteins, PBPs) that recognize the D-Ala-D-Ala motif, blocking peptide cross-linking[4][5].